General Information About Hairy Cell Leukemia

Hairy cell leukemia is a chronic lymphoproliferative disorder that is easily
controlled. The decision to treat is based on symptomatic cytopenias, massive
splenomegaly, or the presence of other complications. About 10% of all
patients will never require therapy.

Untreated hairy cell leukemia is characterized by splenomegaly, varying degrees
of leukopenia (occasionally leukocytosis) and/or pancytopenia, and bone marrow
infiltration by an atypical cell with prominent cytoplasmic projections (i.e., hairy
cells). The bone marrow is usually fibrotic and is not easily aspirated.
Bone marrow biopsies are, therefore, required for diagnosis and evaluation of the
degree of hairy cell infiltration.

Progressive hairy cell leukemia

Progressive hairy cell leukemia, postsplenectomy (or following any systemic
therapy) is characterized by progressive bone marrow replacement by hairy
cells with pancytopenia refractory to treatment. For patients with advanced
hairy cell leukemia treated with cladribine (2-chlorodeoxyadenosine, 2-CdA),
pentostatin, or interferon-alpha, the survival rate appears to be more than 85% at 5 years following the initiation of any one of these therapies.[1][2]

Treatment Option Overview

The initial therapies of choice are either cladribine (2-chlorodeoxyadenosine,
2-CdA) or pentostatin.[1][2] These drugs have comparable response rates but have
not been compared in phase III trials. Cladribine is administered as a one-time continuous infusion or series of subcutaneous injections and is
associated with a high rate of febrile neutropenia.[3][4][5][6] Rarely, more than one
course of treatment is required to induce a desirable response. Treatment
should be discontinued once complete remission or stable partial remission with
normalization of peripheral blood counts is reached. The presence of residual
disease may be predictive of relapse but does not seem to affect survival.[5][7]

The role of consolidation or maintenance therapy in preventing relapse or
progression of the disease following treatment with purine analogs has not been
evaluated and remains unproven. Pentostatin is administered intermittently for
a longer treatment duration but may result in a lower incidence of febrile
complications.[8][9] While most patients remain disease free 10 years after
treatment with these purine analogs, no patient has been followed long enough
to assess cure.[10][11] Both nucleoside analogs cause profound suppression of CD4
counts, which may last for a year, and a potential increased risk of second malignancies has been reported.[5][12]

A study of 3,104 survivors of hairy cell leukemia from the SEER database showed an increased risk of second cancers (standardized incidence ratio = 1.24; 95% CI, 1.11–1.37), especially for Hodgkin and non-Hodgkin lymphomas.[13] The increased risk for second cancers was seen even in the 2 decades prior to the introduction of purine nucleosides.[13] With the use of cladribine, an
increased risk of second malignancies is possible among patients with hairy cell leukemia
(observed to expected ratio of about 1.8 in several series after 6 years).[5][12]
Several series using pentostatin did not report an increased risk of second
malignancies.[8][10][14] For a few patients, such as those with severe
thrombocytopenia, splenectomy might be considered.[15] After splenectomy,
50% of patients will require no additional therapy, and long-term survivors
are common. Therapy with interferon-alpha is another treatment option,
especially for patients with intercurrent infection.[9][16]

Hairy cell leukemia variant has a distinctive phenotype and typically presents with leukocytosis instead of leukopenia.[17] These patients have poorer responses to initial cladribine, shorter durations of response, and typically do not respond again to purine analogues after relapse. Combinations of rituximab and purine analogues are under evaluation and further studies are required to define optimal therapies.[18][19]

Treatment for Hairy Cell Leukemia

Untreated Hairy Cell Leukemia

Hairy cell leukemia is a highly treatable disease. Since it is easily
controlled, many patients have prolonged survival with sequential therapies.
The decision to treat is based on cytopenias (especially if symptomatic),
increasing splenomegaly, indications that the disease is progressing, or the
presence of other, usually infectious complications. It is reasonable to offer
no therapy if the patient is asymptomatic, and blood counts are maintained in an
acceptable range.[1]

Progressive Hairy Cell Leukemia

Standard treatment options:

Cladribine (2-chlorodeoxyadenosine, 2-CdA) given intravenously by continuous
infusion, by daily subcutaneous injections, or by 2-hour infusions daily for 5 to 7 days, results in a complete
response rate of 50% to 80% and an overall response rate of 85% to 95%.[1][2][3][4][5][6][7]
The response rate was lower in 979 patients treated with the Group C mechanism
of the National Cancer Institute (i.e., 50% complete remission rate, 37% partial
remission rate).[3] Responses are durable with this short course of therapy,
and patients who relapse often respond to retreatment with cladribine.[8][9][10] This
drug may cause fever and immunosuppression with documented infection in 33% of treated patients.[3] In a retrospective study of patients with
cladribine-associated neutropenic fever, filgrastim (G-CSF) did not demonstrate
a decrease in the percentage of febrile patients, number of febrile days, or
frequency of admissions for antibiotics.[11] (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes for more infformation on fever.) A potential increased risk for
second malignancies with this agent remains controversial.

Pentostatin given intravenously every other week for 3 to 6 months produces
a 50% to 76% complete response rate and an 80% to 87% overall response
rate.[12][13] Complete remissions are of substantial duration. In two trials
with 9-year median follow-up, relapse-free survival ranged from 56% to
67%.[14][15] Side effects include fever, immunosuppression, cytopenias, and
renal dysfunction. (Refer to the PDQ summary on Fever, Sweats, and Hot Flashes for information on fever.) A randomized comparison of pentostatin and interferon-alpha
demonstrated higher and more durable responses to pentostatin.[12]

Interferon-alpha given subcutaneously 3 times per week for 1 year yields
a 10% complete response rate and an 80% overall response rate. The drug
frequently produces an influenza-like syndrome early in the course of
treatment. Late effects include depression and lethargy. (Refer to the PDQ summary on Depression and for more information on lethargy, refer to the the PDQ summary on Fatigue.) Responding patients
who relapse usually respond to retreatment with interferon-alpha.[16] Remission
can be prolonged with a low-dose maintenance regimen.[17] A randomized
comparison of pentostatin and interferon-alpha demonstrated significantly higher
and more durable responses to pentostatin.[12]

Splenectomy will partially or completely normalize the peripheral blood in
the vast majority of patients with hairy cell leukemia.[18] Usually
little or no change occurs in the bone marrow after splenectomy, and virtually all
patients have progressive disease within 12 to 18 months. Therefore, since a
number of more effective alternatives are available, splenectomy is playing a
decreasing role in the treatment of this disease.

Relapsed or Refractory Hairy Cell Leukemia

Cladribine (2-chlorodeoxyadenosine, 2-CdA) and pentostatin are both highly
efficacious in the treatment of patients with disease refractory to interferon-alpha.[1][2][3][4] Patients who relapse after the first course of cladribine or pentostatin often respond
well to retreatment with the same or another purine analog.[5][6][7][8][9][10] Rituximab can induce durable complete remissions with minimal toxic effects in patients with multiple relapsing or refractory disease after purine analog therapy or after interferon.[11][12][13][14][Level of evidence: 3iiiDiv] The lack of subsequent immunosuppression with rituximab has made this treatment a common choice among relapsing patients in the absence of a clinical trial.[13] Combinations of rituximab with either cladribine or pentostatin are effective in achieving complete remission and are under clinical evaluation.[10][15][16] Both anti-CD25 and anti-CD22 recombinant immunotoxins under clinical evaluation can
induce complete remissions in patients whose disease is resistant to retreatment with purine
analogs or rituximab.[17][18]

Trials (including the ongoing NCT00923013, NCT00321555, and CAT-8015-1001 [NCT00462189] studies, and NCI-04-C-0014, which is now completed) are in the process of evaluating, or have evaluated, new therapies for this group of patients.

Aggressive, high-dose chemotherapy has been beneficial in some cases, but the
associated morbidity and mortality are high. It should not be considered
unless other, more frequently effective therapies have been exhausted.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with
refractory hairy cell leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Changes to This Summary (07/16/2012)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is
editorially independent of NCI. The summary reflects an independent review of
the literature and does not represent a policy statement of NCI or NIH. More
information about summary policies and the role of the PDQ Editorial Boards in
maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of hairy cell leukemia. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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